Chlamydia trachomatis is the most common bacterial sexually transmitted infection in the United States. Approximately 2.5 million chlamydial infections occur in women each year, resulting in pelvic inflammatory disease, ectopic pregnancy, and infertility. Health care costs attributed to chlamydial infections and their sequelae reached $4.2 billion in 1990. Given the prevalence, reproductive consequences, treatment limitations, and economic impact of C. trachomatis and other sexually transmitted infections worldwide, the potential role of topical microbicides in preventing infection must be examined. The major objective of the proposed studies is to investigate the effectiveness of currently available (or newly developed) topical microbicides in preventing or controlling the transmission of cervical chlamydial infection in vivo. We plan to utilize the female pig-tailed macaque animal model for two reasons. First the vaginal flora of the pig-tailed macaque is very similar to humans; second, the model provides a predictable, highly reproducible model for C. trachomatis cervical infection. In addition, we plan to expand upon this model, by developing a non-human primate model for the evaluation of rectally applied topical microbicides for the prevention of rectally acquired chlamydial infection. The specific aims are: 1) assess the effects of a single application of topical microbicide candidates against chlamydial challenge1infection; 2) assess the effects of multiple daily applications of microbicides on vaginal. flora and on cervicovaginal tissues (colposcopy/histology); 3) define a non-human primate model for rectally acquired chlamydial infection. Characterize the normal rectal flora and histology of the pigtailed macaque; and 4) assess the effects of single and multiple applications of microbicide candidates on rectal flora and mucosal tissues. These studies will provide information critical to the design of clinical trials utilizing readily available, inexpensive topical microbicides to protect against transmission of sexually transmitted diseases.